Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.
1] Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA [2] Oak Ridge Institute for Science and Education, Oak Ridge, Tennessee, USA.
Clin Pharmacol Ther. 2014 Aug;96(2):266-77. doi: 10.1038/clpt.2014.87. Epub 2014 Apr 14.
Absorption of an orally administered drug with pH-dependent solubility may be altered when it is coadministered with a gastric acid-reducing agent (ARA). Assessing a drug's potential for pH-dependent drug-drug interactions (DDIs), considering study design elements for such DDI studies, and interpreting and communicating study results in the drug labeling to guide drug dosing are important for drug development. We collected pertinent information related to new molecular entities approved from January 2003 to May 2013 by the US Food and Drug Administration for which clinical DDI studies with ARAs were performed. On the basis of assessments of data on pH solubility and in vivo DDIs with ARAs, we proposed a conceptual framework for assessing the need for clinical pH-dependent DDI studies for weak base drugs (WBDs). Important study design considerations include selection of ARAs and timing of dosing of an ARA relative to the WBD in a DDI study. Labeling implications for drugs having DDIs with ARAs are also illustrated.
当与胃酸降低剂（ARA）共同给药时，具有 pH 依赖性溶解度的口服药物的吸收可能会发生变化。评估药物是否存在 pH 依赖性药物相互作用（DDI）的潜力，考虑此类 DDI 研究的研究设计要素，并在药物标签中解释和传达研究结果以指导药物剂量，这对于药物开发非常重要。我们收集了与 2003 年 1 月至 2013 年 5 月期间美国食品和药物管理局批准的新型分子实体相关的相关信息，这些新型分子实体进行了与 ARAs 的临床 DDI 研究。基于对 pH 溶解度和体内与 ARAs 的 DDI 数据的评估，我们提出了一个用于评估弱碱性药物（WBD）进行临床 pH 依赖性 DDI 研究的需求的概念框架。重要的研究设计考虑因素包括选择 ARAs 和在 DDI 研究中相对于 WBD 给予 ARA 的时间。还说明了与 ARAs 存在 DDI 的药物的标签影响。
